Department of Biochemistry and Biophysics, University of California, San Francisco, San Francisco, CA 94143, United States.
J Immunol Methods. 2010 Jan 31;352(1-2):71-80. doi: 10.1016/j.jim.2009.09.012. Epub 2009 Oct 21.
Telomeres are the DNA-protein complexes that protect the ends of eukaryotic chromosomes. The cellular enzyme telomerase counteracts telomere shortening by adding telomeric DNA. A growing body of literature links shorter telomere length and lower telomerase activity with various age-related diseases and earlier mortality. Thus, leukocyte telomere length (LTL) and telomerase activity are emerging both as biomarkers and contributing factors for age-related diseases. However, no clinical study has directly examined telomerase activity and telomere length in different lymphocyte subtypes isolated from the same donors, which could offer insight into the summary measure of leukocyte telomere maintenance. We report the first quantitative data in humans examining both levels of telomerase activity and telomere length in four lymphocyte subpopulations from the same donors-CD4+, CD8+CD28+ and CD8+CD28- T cells and B cells, as well as total PBMCs-in a cohort of healthy women. We found that B cells had the highest telomerase activity and longest telomere length; CD4+ T cells had slightly higher telomerase activity than CD8+CD28+ T cells, and similar telomere length. Consistent with earlier reports that CD8+CD28- T cells are replicatively senescent cells, they had the lowest telomerase activity and shortest telomere length. In addition, a higher percentage of CD8+CD28- T cells correlated with shorter total PBMC TL (r=-0.26, p=0.05). Interestingly, telomerase activities of CD4+ and CD8+CD28+ T cells from the same individual were strongly correlated (r=0.55, r<0.001), indicating possible common mechanisms for telomerase activity regulation in these two cell subtypes. These data will facilitate the understanding of leukocyte aging and its relationship to human health.
端粒是保护真核染色体末端的 DNA-蛋白质复合物。细胞酶端粒酶通过添加端粒 DNA 来抵消端粒缩短。越来越多的文献将端粒较短和端粒酶活性降低与各种与年龄相关的疾病和更早的死亡率联系起来。因此，白细胞端粒长度 (LTL) 和端粒酶活性既是与年龄相关疾病的生物标志物，也是其促成因素。然而，尚无临床研究直接检查来自同一供体的不同淋巴细胞亚群中的端粒酶活性和端粒长度，这可能有助于深入了解白细胞端粒维持的综合指标。我们报告了第一项在人类中的定量数据，该数据检查了来自同一供体的四个淋巴细胞亚群（CD4+、CD8+CD28+ 和 CD8+CD28- T 细胞和 B 细胞以及总 PBMC）中的端粒酶活性和端粒长度。在一组健康女性中。我们发现 B 细胞具有最高的端粒酶活性和最长的端粒长度；CD4+T 细胞的端粒酶活性略高于 CD8+CD28+T 细胞，而端粒长度相似。与早期报道一致，即 CD8+CD28-T 细胞是复制衰老细胞，它们具有最低的端粒酶活性和最短的端粒长度。此外，较高百分比的 CD8+CD28-T 细胞与较短的总 PBMC TL 相关 (r=-0.26, p=0.05)。有趣的是，同一个体的 CD4+和 CD8+CD28+T 细胞的端粒酶活性具有很强的相关性 (r=0.55, r<0.001)，表明这两种细胞亚型中端粒酶活性调节可能存在共同机制。这些数据将有助于理解白细胞衰老及其与人类健康的关系。
